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- ↵*Address for reprints: Eugene Braunwald, MD, 75 Francis Street, Boston, Massachusetts 02115.
Although it has been known for more than a century that digitalis glycosides exert a powerful beneficial effect on patients with heart failure, atrial fibrillation and a rapid ventricular rate, it was believed for many years that the drug exerts this clinical effect primarily by slowing the heart rate. It was also thought that the extra-cardiac vascular actions of digitalis might be responsible for its therapeutic effect. It has now been established that cardiac glycosides cause arteriolar and venous constriction in a variety of mammalian species including human beings, and that this vasoconstriction involves the coronary vascular bed as well, but it is believed that these actions are not responsible for any beneficial clinical effect. A variety of investigations on cardiac muscle in vitro, anesthetized and conscious dogs and anesthetized and conscious human subjects have shown that cardiac glycosides improve the contractility of failing mammalian myocardium. It has become clear that digitalis also stimulates the contractility of the nonfailing heart. The degree of augmentation of contractility induced by cardiac glycosides is related inversely to the baseline contractile state. Myocardial oxygen consumption, which is increased in the normal heart by the positive inotropic action of glycosides, is actually reduced or remains constant in the failing heart. Cardiac glycosides increase the contractility of the globally ischemic heart, but their actions in chronic ischemic heart disease with regional impairment of function are complex. Deterioration of segmental performance occurs in ischemic and necrotic segments, while improvement of contractility occurs in adjacent normal segments. A modest improvement in left ventricular pump performance occurs in patients with chronic ischemic heart disease with impairment of global left ventricular function.
There has been considerable debate concerning the clinical value of digitalis therapy in heart failure. Simple withdrawal of digitalis resulted in no clinical deterioration in many patients with mild to moderate heart failure. However, in patients with more severe impairment of cardiac function, aggravation of heart failure occurred after digitalis withdrawal, and striking clinical improvement was noted when the drug was readminis-tered. Thus, cardiac glycosides are relatively weak inotropic agents, have a low therapeutic ratio and are moderately effective in heart failure secondary to ventricular volume overload. However, when properly used in patients with severe heart failure and sinus rhythm, particularly in patients with atrial fibrillation, cardiac glycosides improve both cardiac performance and the clinical state and can be administered effectively for years.
- American College of Cardiology Foundation